The significance of differences in fatty acid metabolism between obese and non-obese patients with non-alcoholic fatty liver disease.
Non-alcoholic fatty liver disease (NAFLD) is considered to be associated with metabolic syndrome; however, a number of NAFLD patients are not obese. To explore any differences in lipid metabolism between obese and non-obese patients, we determined the expression of fatty acid metabolism-related genes. Expression levels of target genes were quantified by real-time PCR using liver biopsy samples from NAFLD patients and normal controls. Serum adipocytokine levels were also determined. The expression of genes related to fatty acid synthesis and uptake was generally up-regulated in NAFLD patients; however, no significant difference was seen between obese and non-obese groups. Most of the genes tested related to fatty acid and reactive oxygen species (ROS) elimination, were overexpressed in NAFLD and the levels were significantly higher in non-obese patients. As an exception, peroxisome proliferator-activated receptor alpha expression was suppressed in NAFLD and the levels were lower in the obese group. Triglyceride synthesis-related genes were up-regulated and lipolytic enzymes were decreased in NAFLD, but there was no significant difference between the obese and non-obese groups. In NAFLD, increased de novo synthesis and uptake of fatty acids led to further hepatocyte accumulation of fatty acids. The up-regulation of fatty acid oxidation and the antioxidant pathway and the suppression of lipolysis seemed to be involved in this process. Expression of genes related to fatty acid oxidation and ROS elimination were higher in the non-obese group than in the obese group, which contributes to the trend of more severe liver injury, insulin resistance and steatosis in obese patients.
Nakamuta
Makoto
M
Department of Gastroenterology, Kyushu Medical Center, National Hospital Organization, Fukuoka, Japan.
Kohjima
Motoyuki
M
Higuchi
Nobito
N
Kato
Masaki
M
Kotoh
Kazuhiro
K
Yoshimoto
Tsuyoshi
T
Yada
Masayoshi
M
Yada
Ryoko
R
Takemoto
Ryosuke
R
Fukuizumi
Kunitaka
K
Harada
Naohiko
N
Taketomi
Akinobu
A
Maehara
Yoshihiko
Y
Nakashima
Manabu
M
Enjoji
Munechika
M
D054392:Adipokines / Q000096:biosynthesis / Q000235:genetics; D005227:Fatty Acids / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010084:Oxidation-Reduction; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D054392:Adipokines; D005227:Fatty Acids; D017382:Reactive Oxygen Species